| First Author | Chopin M | Year | 2013 |
| Journal | J Exp Med | Volume | 210 |
| Issue | 13 | Pages | 2967-80 |
| PubMed ID | 24249112 | Mgi Jnum | J:266811 |
| Mgi Id | MGI:6155394 | Doi | 10.1084/jem.20130930 |
| Citation | Chopin M, et al. (2013) Langerhans cells are generated by two distinct PU.1-dependent transcriptional networks. J Exp Med 210(13):2967-80 |
| abstractText | Langerhans cells (LCs) are the unique dendritic cells found in the epidermis. While a great deal of attention has focused on defining the developmental origins of LCs, reports addressing the transcriptional network ruling their differentiation remain sparse. We addressed the function of a group of key DC transcription factors-PU.1, ID2, IRF4, and IRF8-in the establishment of the LC network. We show that although steady-state LC homeostasis depends on PU.1 and ID2, the latter is dispensable for bone marrow-derived LCs. PU.1 controls LC differentiation by regulating the expression of the critical TGF-beta responsive transcription factor RUNX3. PU.1 directly binds to the Runx3 regulatory elements in a TGF-beta-dependent manner, whereas ectopic expression of RUNX3 rescued LC differentiation in the absence of PU.1 and promoted LC differentiation from PU.1-sufficient progenitors. These findings highlight the dual molecular network underlying LC differentiation, and show the central role of PU.1 in these processes. |
